Details for Patent: 9,580,424

Title:	Crystalline forms of trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide sodium salt
Abstract:	The present invention relates to novel crystalline forms of sodium salt of trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide (e.g., NXL-104) thereof. The present invention relates to compositions comprising a crystalline form of sodium salt of trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide (e.g., NXL-104) alone or in combination with an antibacterial agent (e.g., ceftaroline fosamil). Processes for the preparation of the crystalline forms and methods of treating bacterial infections by administering the crystalline forms alone or in combination with an antibacterial agent (e.g., ceftaroline fosamil) are also described.
Inventor(s):	Dedhiya; Mahendra G. (Pomona, NY), Bhattacharya; Sisir (Commack, NY), Ducandas; Veronique (Vitry sur Seine, FR), Giuliani; Alexandre (Villecresnes, FR), Ravaux; Valerie (Reyrieux, FR), Bonnet; Alain (Chateau-Thierry, FR), Priour; Alain (Paris, FR), Spargo; Peter (Deal, GB)
Assignee:	Forest Laboratories Holdings Limited (Hamilton, BM)
Filing Date:	May 13, 2015
Application Number:	14/711,162
Claims:	1. A pharmaceutical composition comprising a crystalline form of trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide or a pharmaceutically acceptable salt thereof and ceftaroline or a prodrug of ceftaroline, wherein the composition comprises less than about 0.6% of a compound of Formula (III): ##STR00020## 2. The crystalline form according to claim 1, wherein the salt is a sodium salt of (1R,2S,5R)-7-oxo-6-sulphooxy-1,6-diazabicyclo[3.2.1]octane-2-carboxamide. 3. The crystalline form according to claim 2, wherein the crystalline form has an X-Ray powder diffraction pattern comprising a characteristic peak at about 13.0+/-0.5 degrees 2.theta.. 4. The crystalline form according to claim 2, wherein the crystalline form has an X-Ray powder diffraction pattern comprising a characteristic peak at about 16.5+/-0.5 degrees 2.theta.. 5. The crystalline form according to claim 2, wherein the crystalline form has an X-Ray powder diffraction pattern comprising a characteristic peaks at about 17.5+/-0.5 degrees 2.theta.. 6. The crystalline form according to any one of claims 3 to 5, wherein the crystalline form has an X-Ray powder diffraction pattern further comprising a characteristic peak at about 17.3; about 22.3+/-0.5 degrees 2.theta. or a combination thereof. 7. The crystalline form according to any one of claims 3 to 5, wherein the crystalline form has an X-Ray powder diffraction pattern further comprising a characteristic peak at about 19.2; about 19.5+/-0.5 degrees 2.theta. or a combination thereof. 8. The crystalline form according to any one of claims 3 to 5, wherein the crystalline form has an X-Ray powder diffraction pattern further comprising a characteristic peak at about 19.9; about 22.0; about 25.2; about 28.2+/-0.5 degrees 2.theta. or a combination thereof. 9. The crystalline form according to any one of claims 3 to 5, wherein the crystalline form has an X-Ray powder diffraction pattern further comprising a characteristic peak at about 23.2; about 30.2; about 30.9; about 36.1+/-0.5 degrees 2.theta. or a combination thereof. 10. The crystalline form according to claim 1, wherein the crystalline form has an X-Ray powder diffraction pattern comprising a characteristic peak at about 13.0; about 16.5; about 17.3; about 17.5; about 19.2; about 19.5; about 19.9; about 22.0; about 22.3; about 25.2; about 28.2+/-0.5 degrees 2.theta. or a combination thereof. 11. The crystalline form according to claim 1, wherein the crystalline form has an X-Ray powder diffraction pattern comprising characteristic peaks at about 13.0; about 16.5; about 17.3; about 17.5; about 19.2; about 19.5; about 19.9; about 22.0; about 22.3; about 23.2; about 25.2; about 28.2; about 30.2; about 30.9 and about 36.1+/-0.5 degrees 2.theta.. 12. The crystalline form according to claim 2, wherein the crystalline form has an X-Ray powder diffraction pattern comprising a d-spacing value at about 6.8+/-2 nm. 13. The crystalline form according to claim 2, wherein the crystalline form has an X-Ray powder diffraction pattern comprising a d-spacing value at about 5.1+/-2 nm. 14. The crystalline form according to claim 2, wherein the crystalline form has an X-Ray powder diffraction pattern comprising a d-spacing value at about 5.4+/-2 nm. 15. The crystalline form according any one of claims 12 to 14, wherein the crystalline form has an X-Ray powder diffraction pattern further comprising a d-spacing value at about 3.2; about 3.5; about 4.0; about 4.5; about 4.6+/-2 nm or a combination thereof. 16. The crystalline form according to claim 1, wherein the crystalline form has an X-Ray powder diffraction pattern comprising d-spacing values at about 2.5; about 2.9; about 3.0; about 3.2; about 3.5; about 3.8; about 4.0; about 4.5; about 4.6; about 5.1; about 5.4; about 6.8+/-2 nm or a combination thereof. 17. The crystalline form according to claim 1, wherein the crystalline form has an X-Ray powder diffraction pattern comprising d-spacing values at about 2.5; about 2.9; about 3.0; about 3.2; about 3.5; about 3.8; about 4.0; about 4.5; about 4.6; about 5.1; about 5.4; and about 6.8+/-2 nm. 18. A pharmaceutical composition comprising a crystalline form of trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide or a pharmaceutically acceptable salt thereof. 19. A pharmaceutical composition comprising a crystalline form of a sodium salt of (1R,2S,5R)-7-oxo-6-sulphooxy-1,6-diazabicyclo[3.2.1]octane-2-carboxamide according to any one of claims 3 to 5. 20. A composition comprising about 200 mg to about 1200 mg of a crystalline form of trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide or a pharmaceutically acceptable salt thereof and ceftaroline or a prodrug of ceftaroline, wherein the composition provides an in vivo plasma profile for the crystalline form comprising a mean Cmax of less than about 100 ug/ml, and the composition comprises less than about 0.6% of a compound of Formula (III): ##STR00021## 21. The composition according to claim 20 wherein the composition comprises the sodium salt of (1R,2S,5R)-7-oxo-6-sulphooxy-1,6-diazabicyclo[3.2.1]octane-2-carboxamide. 22. The composition according to claim 20, wherein the composition comprises about 400 mg of sodium salt of (1R,2S,5R)-7-oxo-6-sulphooxy-1,6-diazabicyclo[3.2.1]octane-2-carboxamide. 23. The composition according to claim 20, wherein the composition comprises about 600 mg of sodium salt of (1R,2S,5R)-7-oxo-6-sulphooxy-1,6-diazabicyclo[3.2.1]octane-2-carboxamide. 24. The composition according to claim 20, wherein the composition comprises Form I of said crystalline form. 25. The composition according to claim 20, wherein the in vivo plasma profile comprises a mean Cmax of about 10 to 50 ug/ml. 26. The composition according to claim 20, further comprising about 200 mg to 1200 mg of ceftaroline or a prodrug of ceftaroline wherein the composition provides an in vivo plasma profile for ceftaroline comprising a mean Cmax of less than about 100 ug/ml. 27. The composition according to claim 26, wherein the composition comprises about 400 mg ceftaroline fosamil. 28. The composition according to claim 26, wherein the composition comprises about 600 mg ceftaroline fosamil. 29. The composition according to any one of claim 27 or 28, wherein the composition comprises ceftaroline fosamil monohydrate acetic acid solvate. 30. A composition comprising about 200 mg to 1200 mg of a crystalline form of trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxa- mide or a pharmaceutically acceptable salt thereof and ceftaroline or a prodrug of ceftaroline, wherein the composition provides an in vivo plasma profile for the crystalline form comprising a mean AUC.sub.0-.infin. of more than about 10 ug h/ml, and the composition comprises less than about 0.6% of a compound of Formula (III): ##STR00022## 31. The composition according to claim 30, wherein the composition comprises the sodium salt of sodium salt of (1R,2S,5R)-7-oxo-6-sulphooxy-1,6-diazabicyclo[3.2.1]octane-2-carboxamide. 32. The composition according to claim 30, wherein the composition comprises about 400 mg of sodium salt of (1R,2S,5R)-7-oxo-6-sulphooxy-1,6-diazabicyclo[3.2.1]octane-2-carboxamide. 33. The composition according to claim 30, wherein the composition comprises about 600 mg of sodium salt of (1R,2S,5R)-7-oxo-6-sulphooxy-1,6-diazabicyclo[3.2.1]octane-2-carboxamide. 34. The composition according to claim 30, wherein the composition comprises Form I of said crystalline form. 35. The composition according to claim 30, wherein the in vivo plasma profile comprises a mean AUC.sub.0-.infin. of about 10 to 200 ug h/ml. 36. The composition according to claim 30, further comprising about 200 mg to 1200 mg of ceftaroline or a prodrug of ceftaroline wherein the composition provides an in vivo plasma profile for ceftaroline comprising a mean AUC.sub.0-.infin. of more than about 10 ug h/ml. 37. The composition according to claim 36, wherein the composition comprises about 400 mg ceftaroline fosamil. 38. The composition according to claim 36, wherein the composition comprises about 600 mg ceftaroline fosamil. 39. The composition according to any one of claim 37 or 38, wherein the composition comprises ceftaroline fosamil monohydrate acetic acid solvate. 40. A composition comprising about 200 mg to 1200 mg of a crystalline form of trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxa- mide or a pharmaceutically acceptable salt thereof wherein the composition provides an in vivo plasma profile for the crystalline form comprising a mean Tmax of more than about 10 minutes. 41. The composition according to claim 40, wherein the composition comprises the sodium salt of (1R,2S,5R)-7-oxo-6-sulphooxy-1,6-diazabicyclo[3.2.1]octane-2-carboxamide. 42. The composition according to claim 40, wherein the composition comprises about 400 mg of sodium salt of (1R,2S,5R)-7-oxo-6-sulphooxy-1,6-diazabicyclo[3.2.1]octane-2-carboxamide. 43. The composition according to claim 40, wherein the composition comprises about 600 mg of sodium salt of (1R,2S,5R)-7-oxo-6-sulphooxy-1,6-diazabicyclo[3.2.1]octane-2-carboxamide. 44. The composition according to claim 40, wherein the composition comprises Form I of said crystalline form. 45. The composition according to claim 40, wherein the in vivo plasma profile comprises a mean Tmax of about 30 minutes to about 2 hours. 46. The composition according to claim 40, further comprising about 200 mg to 1200 mg of ceftaroline or a prodrug of ceftaroline wherein the composition provides an in vivo plasma profile for ceftaroline comprising a mean Tmax of more than about 10 minutes. 47. The composition according to claim 36, wherein the composition comprises about 400 mg ceftaroline fosamil. 48. The composition according to claim 36, wherein the composition comprises about 600 mg ceftaroline fosamil. 49. The composition according to anyone of claim 37 or 38, wherein the composition comprises ceftaroline fosamil monohydrate acetic acid solvate. 50. The crystalline form according to claim 2, wherein the crystalline form is Form II. 51. The crystalline form according to claim 2, wherein the crystalline form has an X-Ray powder diffraction pattern comprising a characteristic peak at about 17.1+/-0.5 degrees 2.theta.. 52. The crystalline form according to claim 2, wherein the crystalline form has an X-Ray powder diffraction pattern comprising a characteristic peak at about 16.4+/-0.5 degrees 2.theta.. 53. The crystalline form according to claim 2, wherein the crystalline form has an X-Ray powder diffraction pattern comprising a characteristic peak at about 8.5+/-0.5 degrees 2.theta.. 54. A composition comprising the crystalline form according to any one of claims 51 to 53.